MYO1F positions cGAS on the plasma membrane to ensure full and functional signaling

Heping Wang¹, Zhihui Cui¹, Wanwei Sun¹, Ming Yi², Yuheng Cheng³, Yunpeng Zhang³, Yanyun Du², Ting Pan⁴, Ru Gao¹, Lingyun Feng², Bo Zeng², Guoling Huang⁴, Yangyang Li², Yuan Wang⁴, Cun-Jin Zhang⁵, Ruirui He⁶, Chenhui Wang⁷

Affiliations

¹ Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, 430074 Wuhan, China; The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 611731 Chengdu, China.
² The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 611731 Chengdu, China; Sichuan Medical Laboratory Clinical Medical Research Center, Sichuan Provincial People's Hospital, 611731 Chengdu, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China.
³ Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
⁴ School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China.
⁵ School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China; Department of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 610072 Chengdu, China.
⁶ The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 611731 Chengdu, China; Sichuan Medical Laboratory Clinical Medical Research Center, Sichuan Provincial People's Hospital, 611731 Chengdu, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China. Electronic address: heruirui0628@uestc.edu.cn.
⁷ The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 611731 Chengdu, China; Sichuan Medical Laboratory Clinical Medical Research Center, Sichuan Provincial People's Hospital, 611731 Chengdu, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China. Electronic address: wangch@uestc.edu.cn.

PMID: 39694035
DOI: 10.1016/j.molcel.2024.11.026

MYO1F positions cGAS on the plasma membrane to ensure full and functional signaling

Heping Wang et al. Mol Cell. 2025.

. 2025 Jan 2;85(1):150-165.e7.

doi: 10.1016/j.molcel.2024.11.026. Epub 2024 Dec 17.

Authors

Affiliations

¹ Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, 430074 Wuhan, China; The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 611731 Chengdu, China.
² The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 611731 Chengdu, China; Sichuan Medical Laboratory Clinical Medical Research Center, Sichuan Provincial People's Hospital, 611731 Chengdu, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China.
³ Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
⁴ School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China.
⁵ School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China; Department of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 610072 Chengdu, China.
⁶ The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 611731 Chengdu, China; Sichuan Medical Laboratory Clinical Medical Research Center, Sichuan Provincial People's Hospital, 611731 Chengdu, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China. Electronic address: heruirui0628@uestc.edu.cn.
⁷ The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 611731 Chengdu, China; Sichuan Medical Laboratory Clinical Medical Research Center, Sichuan Provincial People's Hospital, 611731 Chengdu, China; Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China. Electronic address: wangch@uestc.edu.cn.

PMID: 39694035
DOI: 10.1016/j.molcel.2024.11.026

Abstract

Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) detects viral or endogenous DNA, activating the innate immune response to infections and autoimmune diseases. Upon binding to double-stranded DNA, cGAS synthesizes 2'3' cGMP-AMP, which triggers type I interferon production. Besides its presence in the cytosol and nucleus, cGAS is found at the plasma membrane, although its significance remains unclear. Here, we report that cGAS associates with myosin 1F (MYO1F) at the plasma membrane of human and mouse macrophages. During viral infection, phosphorylation of MYO1F by spleen-associated tyrosine kinase (SYK) facilitates the recruitment of lysine acetyltransferase 2A (KAT2A), which acetylates cGAS at lysine residues 421, 292, and 131, essential for its activation. Moreover, membrane-localized cGAS is crucial for signaling activation and type I interferon production triggered by virus-cell fusion due to Mn²⁺ release from organelles. Our results highlight the importance of MYO1F-mediated cGAS localization for its full activation in response to viral infection.

Keywords: MYO1F; acetylation; antiviral immunity; cGAS; cGAS-STING; membrane localization; virus-cell membrane fusion.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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MYO1F positions cGAS on the plasma membrane to ensure full and functional signaling

Affiliations

MYO1F positions cGAS on the plasma membrane to ensure full and functional signaling

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Molecular Biology Databases

Research Materials

Miscellaneous